The long term goals of this project are to understand the interactions of neural and immune systems in the development of severe childhood psychopathology, especially infantile autism. This application focuses on antibody mediated immunity with the specific hypothesis that some individuals develop infantile autism as the result of autoantibodies to high affinity serotonin receptors. These autoantibodies are hypothesized to interfere with the developmental processes of neurogenesis and synaptogenesis. In addition, it is proposed that individuals with relatively low immunoglobulin IgG levels are at increased risk for developing anti-receptor autoantibodies and that these low IgG levels are genetically determined. This application contains three distinct but overlapping projects: 1) a population study of the occurrence and nature of immune abnormalities in infantile autism, 2) a twin study of the occurrence of immune abnormalities in infantile autism, and 3) an in vitro pathophysiology study of the effects of anti-serotonin receptor antibodies on neural development and serotonin receptor subtype function. Projects 1, 2, and 3 will share study samples and utilize the same preparative procedures and assays of antibody subtype, specificity, and effect. Project 3 will also use samples from locally identified individuals. The specific experimental aims are: 1) establish the antibody nature and prevalence of factors which inhibit in vitro ligand binding to serotonin receptors; 2) replicate the presence of low IgG subclass antibody levels in autistic individuals by radialimmunodiffusion; 3) assess the genetic contribution to the presence of anti-serotonin receptor antibodies and low IgG subclass levels in autism by measuring these parameters in a sample of twins; and 4) determine the effect of antibodies from autistic and control children on serotonin receptor number and function in an in vitro neuronal culture system. These studies will test genetic and immunopathological hypotheses about the etiology of autism and may provide the tools for the development of in vitro and in vivo model systems of autism.